DRD1 associations with smoking abstinence across slow and normal nicotine metabolizers.
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ABSTRACT:
SUBMITTER: Lee W
PROVIDER: S-EPMC3376177 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
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DRD1 associations with smoking abstinence across slow and normal nicotine metabolizers.
Lee Wonho W Ray Riju R Bergen Andrew W AW Swan Gary E GE Thomas Paul P Tyndale Rachel F RF Benowitz Neal L NL Lerman Caryn C Conti David V DV
Pharmacogenetics and genomics 20120701 7
Nicotine metabolism and genetic variation have an impact on nicotine addiction and smoking abstinence; however, further research is required. The nicotine metabolite ratio (NMR) is a robust biomarker of nicotine metabolism used to categorize slow and normal nicotine metabolizers (lower 25th quartile cut off). In two randomized clinical trials of smoking abstinence treatments, we conducted NMR-stratified analyses on smoking abstinence across 13 regions coding for nicotinic acetylcholine receptors ...[more]
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Project description:ImportanceThe US Food and Drug Administration (FDA) has announced its intention to reduce the nicotine content in combustible cigarettes but must base regulation on public health benefits. Fast nicotine metabolizers may be at risk for increased smoking following a national nicotine reduction policy. We hypothesized that using reduced nicotine content (RNC) cigarettes would be associated with increases in smoking behaviors and exposure among smokers with a fast-but not slow-nicotine-metabolite ratio (NMR).ObjectivesTo examine the association of RNC cigarettes with smoking behaviors and biomarkers of exposure and to compare these associations in fast and slow metabolizers of nicotine based on the NMR.Design setting and participantsA 35-day, 3-period, within-participant nonrandomized clinical trial was conducted at an academic medical center in Philadelphia, Pennsylvania. A 5-day baseline period using the smokers' preferred brand of cigarettes was followed by 2 consecutive 15-day periods using free investigational RNC cigarettes. A total of 100 daily, non-treatment-seeking, nonmenthol cigarette smokers (59 fast, 41 slow metabolizers) were recruited from December 24, 2013, to December 2, 2015. Data analysis was performed from December 12, 2016, to January 3, 2018.InterventionsTwo 15-day periods using cigarettes containing 5.2 mg (RNC1) and 1.3 mg (RNC2) of nicotine per gram of tobacco.Main outcomes and measuresSmoking behaviors (number of cigarettes per day [CPD], total puff volume) and biomarkers of exposure (carbon monoxide [CO], urine total nicotine equivalents [TNE], and 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]).ResultsSmokers (73 [73.0%] men; 74 [74.0%] white; mean [SD] age, 43.02 [12.13] years; mean [SD] CPD, 17.31 [5.72]) consumed 2.62 (95% CI, 1.54-3.70) more CPD during the RNC1 period vs their preferred brand during baseline (P < .001) and approximated baseline CPD during the RNC2 period (mean difference, 0.96 [95% CI, -0.36 to 2.28]; P = .24). Additional outcome measures were lower during both RNC periods vs baseline (total puff volume, mean [95% CI]: RNC1, 537 mL [95% CI, 479-595 mL]; RNC2, 598 mL [95% CI, 547-649 mL] vs baseline, 744 mL [95% CI, 681-806 mL]; TNE, mean [95% CI]: RNC1, 30.9 nmoL/mg creatinine [95% CI, 26.0-36.6 nmoL/mg]; RNC2, 22.8 nmoL/mg creatinine [95% CI, 17.8-29.0 nmoL/mg] vs baseline, 54.6 nmoL/mg creatinine [95% CI, 48.1-62.1 nmoL/mg]; and NNAL, mean [95% CI]: RNC1, 229 pg/mg creatinine [95% CI, 189-277 pg/mg]; RNC2, 190 pg/mg creatinine [95% CI, 157-231 pg/mg] vs baseline, 280 pg/mg creatinine [95% CI, 231-339 pg/mg]; all P < .001). Carbon monoxide measures were similar across study periods (CO boost [SD], RNC1, 4.6 ppm [4.1-5.1 ppm]; RNC2, 4.2 ppm [3.7-4.6 ppm]; and baseline, 4.4 ppm [3.8-4.9 ppm]). The RNC cigarette associations did not differ by NMR.Conclusions and relevanceBoth RNC cigarettes were associated with decreased puffing and urinary biomarker exposure but not with decreased daily cigarette consumption or CO levels. The NMR did not moderate associations at the nicotine levels tested, suggesting that fast metabolizers may not be at greater risk of increasing use or exposure from these products should the FDA mandate an RNC standard for cigarettes.
| S-EPMC6322845 | biostudies-literature
Project description:INTRODUCTION:The Intolerance for Smoking Abstinence Discomfort Questionnaire (IDQ-S) assesses distress tolerance specific to nicotine withdrawal. Though developed to assess withdrawal-related distress, the IDQ-S has not been validated among nicotine-deprived, treatment-seeking smokers. The present study extended previous research by examining the predictive utility of the IDQ-S among abstinent, motivated-to-quit smokers. METHODS:Abstinent, treatment-seeking smokers completed the IDQ-S Withdrawal Intolerance and Lack of Cognitive Coping scales, assessments of nicotine dependence and reinforcement, and smoking history at baseline. At baseline and at 24-h, 2-week, and 1-month follow-up, participants completed a smoking cue-reactivity task (collection of cue-elicited craving and negative affect), and assessments of cigarettes per day (CPD; daily diaries at follow-up), carbon monoxide (CO), and cotinine. RESULTS:Greater IDQ-S Withdrawal Intolerance was associated with younger age, higher nicotine dependence and reinforcement, and less smoking years (ps?<?.03). Greater IDQ-S Lack of Cognitive Coping was associated with less education, lower nicotine dependence and reinforcement, higher baseline CPD, and no prior quit attempts (ps?<?.04). IDQ-S scales did not significantly predict cue-elicited craving or negative affect, CPD, CO, or cotinine levels at follow-up (ps?>?.10). CONCLUSIONS:Withdrawal intolerance and lack of cognitive coping did not predict smoking outcomes among nicotine-deprived, treatment-seeking smokers, but were associated with smoking characteristics, including nicotine dependence and reinforcement. Withdrawal intolerance and lack of cognitive coping may not be especially useful in predicting craving and smoking behavior, but future studies should replicate the present study's findings and assess the stability of the IDQ-S before forming firm conclusions about its predictive utility.
| S-EPMC5975182 | biostudies-literature
Project description:Nicotine addiction is associated with dysregulated inhibitory control (IC), mediated by corticothalamic circuitry including the right inferior frontal gyrus (rIFG). Among sated smokers, worse IC task performance and greater IC-related rIFG activity have been shown to be associated with greater relapse vulnerability. The present study investigated the effects of smoking abstinence on associations between IC task performance, rIFG activation, and smoking behavior. Smokers (N = 26, 15 female) completed an IC task (Go/Go/No-go) during fMRI scanning followed by a laboratory-based smoking relapse analog task (SRT) on two visits: once when sated and once following 24 h of smoking abstinence. During the SRT, smokers were provided with monetary rewards for incrementally delaying smoking. A significant main effect of No-go accuracy on latency to smoke during the SRT was observed when collapsing across smoking states (abstinent vs. sated). Similarly, a significant main effect of IC-related activation in rIFG on SRT performance was observed across states. The main effect of state, however, was non-significant in both of these models. Furthermore, the interaction between smoking state and No-go accuracy on SRT performance was non-significant, indicating a similar relationship between IC and lapse vulnerability under both sated and abstinent conditions. The state X rIFG activation interaction on SRT performance was likewise non-significant. Post-hoc whole brain analyses indicated that abstinence resulted in greater IC-related activity in the right middle frontal gyrus (MFG) and insula. Activation during IC in these regions was significantly associated with decreased No-go accuracy. Moreover, greater abstinence induced activity in right MFG during IC was associated with smoking sooner on the SRT. These findings are bolstered by the extant literature on the effects of nicotine on executive function and also contribute novel insights on how individual differences in behavioral and neuroimaging measures of IC may influence relapse propensity independent of smoking state.
| S-EPMC8047070 | biostudies-literature
Project description:IntroductionSmokers discount delayed rewards steeper than non-smokers or ex-smokers, possibly due to neuropharmacological effects of tobacco on brain circuitry, or lower abstinence rates in smokers with steep discounting. To delineate both theories from each other, we tested if temporal discounting, choice inconsistency, and related brain activity in treatment-seeking smokers (1) are higher compared to non-smokers, (2) decrease after smoking cessation, and (3) predict relapse.MethodsAt T1, 44 dependent smokers, 29 non-smokers, and 30 occasional smokers underwent fMRI while performing an intertemporal choice task. Smokers were measured before and 21 days after cessation if abstinent from nicotine. In total, 27 smokers, 28 non-smokers, and 29 occasional smokers were scanned again at T2. Discounting rate k and inconsistency var(k) were estimated with Bayesian analysis.ResultsFirst, k and var(k) in smokers in treatment were not higher than in non-smokers or occasional smokers. Second, neither k nor var(k) changed after smoking cessation. Third, k did not predict relapse, but high var(k) was associated with relapse during treatment and over 6 months. Brain activity in valuation and decision networks did not significantly differ between groups and conditions.ConclusionOur data from treatment-seeking smokers do not support the pharmacological hypothesis of pronounced reversible changes in discounting behavior and brain activity, possibly due to limited power. Behavioral data rather suggest that differences between current and ex-smokers might be due to selection. The association of choice consistency and treatment outcome possibly links consistent intertemporal decisions to remaining abstinent.
| S-EPMC7826310 | biostudies-literature
Project description:Preclinical and clinical literature suggest that sex hormones impact tobacco use behaviors in women. The goal of this double-blind crossover laboratory study was to examine the effect of oral exogenous progesterone (200 mg twice per day) versus placebo on nicotine response using measures of motor speed and cognitive function in women following overnight smoking abstinence. We hypothesized that increased progesterone would blunt the nicotine response whereby producing less change in motor speed and cognition in response to nicotine exposure. Female smokers, age 18-35, were randomized to participate in two 9-day crossover testing weeks. Participants completed a lab session following overnight abstinence where they were administered nicotine nasal spray and asked to complete measures of immediate memory (IMT), delayed memory (DMT), word recall (WR), and finger tapping speed (FT). After the first 9-day testing week, participants resumed smoking and returned the following month to complete the identical lab session in the crossover condition. Forty-seven women were included in this analysis (n = 47). We found no differences in the magnitude of response for IMT, DMT, and WR between conditions. For FT, women had a blunted response to nicotine during the placebo condition. When examining the association between hormone levels and relative performance, we found increases in DMT, WR, and FT but decreases in IMT during the progesterone condition. We observed differences between progesterone versus placebo in relative change in some measures of nicotine response following overnight abstinence. Future studies are needed to further characterize this response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Project description:This study investigated the influence of the rate of nicotine metabolism, as indicated by the nicotine metabolite ratio (NMR), on tobacco dependence. We stratified 136 smokers on the basis of saliva NMR as fast (n = 65) and slow (n = 71) metabolizers. Two "loading cigarettes" were smoked after overnight, and a "reward cigarette" was smoked after 6 hours of daytime, abstinence. Blood nicotine concentrations, expired carbon monoxide, withdrawal/craving, and reward questionnaires were collected before/after smoking and during daytime abstinence. Compared with slow metabolizers, fast metabolizers had a shorter nicotine elimination half-life (P < 0.001), lower plasma nicotine concentrations (P < 0.001), and higher withdrawal/craving scores (P < 0.05) for most times during daytime abstinence, indicating that fast metabolizers are likely smoking more to relieve withdrawal symptoms (negative reinforcement). Reward/satisfaction scores were similar in fast and slow metabolizers, suggesting that faster nicotine metabolism, assessed by NMR, is not associated with greater positive reinforcement. CYP2A6 normal (n = 82) and reduced (n = 42) genotype predicted plasma nicotine concentrations but not withdrawal symptoms.
| S-EPMC7967935 | biostudies-literature
Project description:INTRODUCTION:The decrease in smoking rates in North America has plateaued, underscoring the need for new approaches to treat nicotine dependence. Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. A phenotypic measure of CYP2A6 activity is the nicotine metabolite ratio (NMR), the ratio of 3'hydroxycotinine/cotinine. The NMR is associated with smoking cessation. However, the NMR is also associated with genetic (eg, CYP2A6 genotype) and other (eg, sex and ethnicity) factors. Here we aimed to determine if previously identified non-CYP2A6 sources of variation in the NMR mitigated the association between the NMR and short-term abstinence. METHODS:The NMR was determined from blood samples collected at intake from daily smokers aged 18-65. Biochemically-verified point prevalence abstinence (exhaled carbon monoxide level ? 8 ppm) was measured at 1 week following the target quit date in participants from a smoking cessation clinical trial (NCT01314001). Analyses were restricted to N = 462 blacks and N = 693 whites in the intent-to-treat sample. RESULTS:Lower NMR (<0.31) was associated with a higher likelihood of 1-week abstinence (OR = 1.43; 95% CI = 1.12, 1.84). NMR was associated with abstinence even after controlling for treatment arm (nicotine patch or varenicline) and factors previously associated with NMR variation including sex, ethnicity, estrogen-containing hormonal therapy, body mass index, alcohol, and cigarette consumption. CONCLUSIONS:NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence.
| S-EPMC6220835 | biostudies-literature
Project description:Abstinence reinforcement is efficacious for improving smoking treatment outcomes, but practical constraints related to the need for multiple in-person carbon monoxide (CO) breath tests daily to verify smoking abstinence have limited its use. This study tested an mHealth procedure to remotely monitor and reinforce smoking abstinence in individuals' natural environment.Eligible treatment-seeking smokers (N = 90) were randomized to (1) usual care and ecological monitoring with abstinence reinforcement (mHealth reinforcement) or (2) without reinforcement (mHealth monitoring). Usual care was 8 weeks of transdermal nicotine and twice-weekly telephone counseling. Following training, an interactive voice response system prompted participants to conduct CO tests 1-3 daily at pseudorandom times (7 am to 10 pm) for 4 weeks. When prompted, participants used a study cell phone and CO monitor to complete a CO self-test, video record the process, and submit videos using multimedia messaging. mHealth reinforcement participants could earn prizes for smoking-negative on-time CO tests. The interactive voice response generated preliminary earnings immediately. Earnings were finalized by comparing video records against participants' self-reports.mHealth reinforcement was associated with a greater proportion of smoking-negative CO tests, longest duration of prolonged abstinence, and point-prevalence abstinence during the monitoring/reinforcement phase compared to mHealth monitoring (p < .01, d = 0.8-1.3). Follow-up (weeks 4-24) analyses indicated main effects of reinforcement on point-prevalence abstinence and proportion of days smoked (p ? .05); values were comparable by week 24.mHealth reinforcement has short-term efficacy. Research on methods to enhance and sustain benefits is needed.This study suggests that mHealth abstinence reinforcement is efficacious and may present temporal and spatial opportunities to research, engage, and support smokers trying to quit that do not exist with conventional (not technology-based) reinforcement interventions.
| S-EPMC6075519 | biostudies-literature
Project description:IntroductionPsychological, physiological and social factors play an important role in the initiation, persistence, dependence and relapse of smoking behaviors, and coping style and smoking abstinence self-efficacy can all affect nicotine dependence.MethodsA cross-sectional sample of 568 quitters from 19 communities in Beijing in 2019 was surveyed. Demographic information and psychological characteristics of smokers were collected by an interview questionnaire, and psychological traits scales including the Smoking Abstinence Self-Efficacy (SASE) and the Trait Coping Style Questionnaire (TCSQ). We compared differences in psychological traits across demographic information and explored the relationship between nicotine dependence and coping styles and self-efficacy in refusing to smoke.ResultsSignificant differences were identified in self-efficacy in refusing to smoke and across dimensions among quitters by gender, job type, education level, and monthly income level (all p<0.05). Males had lower self-efficacy in the habitual/addictive context than females; retirees had better overall self-efficacy and self-efficacy in the negative/emotional context than business service workers and professionals; and high-educated, high-income quitters had lower self-efficacy in the negative/emotional context. There are significant differences in positive coping styles among quitters of different ages, levels of education, and types of work (all p<0.05). The results further showed that the underage population, highly educated population, and practitioners other than those in retirement, are less likely to use positive coping styles. Interventional effects analysis showed that a higher sense of self-efficacy in addictive contexts can counteract some of the negative coping styles that induce smoking.ConclusionsSelf-efficacy played an indirect mediating role between negative coping style and nicotine dependence; individuals who used more negative coping styles were more likely to engage in smoking and therefore were more nicotine dependent. Hence, it is necessary to reduce the use of negative coping strategies and improve the self-efficacy of smoking abstinence in the face of addiction.
| S-EPMC7485440 | biostudies-literature
Project description:ObjectiveTo examine the effectiveness of a nicotine patch worn for four weeks before a quit attempt.DesignRandomised controlled open label trial.SettingPrimary care and smoking cessation clinics in England, 2012-15.Participants1792 adults who were daily smokers with tobacco dependence. 899 were allocated to the preloading arm and 893 to the control arm.InterventionsParticipants were randomised 1:1, using concealed randomly permuted blocks stratified by centre, to either standard smoking cessation pharmacotherapy and behavioural support or the same treatment supplemented by four weeks of 21 mg nicotine patch use before quitting: "preloading."Main outcome measuresThe primary outcome was biochemically confirmed prolonged abstinence at six months. Secondary outcomes were prolonged abstinence at four weeks and 12 months.ResultsBiochemically validated abstinence at six months was achieved by 157/899 (17.5%) participants in the preloading arm and 129/893 (14.4%) in the control arm: difference 3.0% (95% confidence interval -0.4% to 6.4%), odds ratio 1.25 (95% confidence interval 0.97 to 1.62), P=0.08 in the primary analysis. There was an imbalance between arms in the frequency of varenicline use as post-cessation treatment, and planned adjustment for this gave an odds ratio for the effect of preloading of 1.34 (95% confidence interval 1.03 to 1.73), P=0.03: difference 3.8% (0.4% to 7.2%). At four weeks, the difference in prolonged abstinence unadjusted for varenicline use was odds ratio 1.21 (1.00 to 1.48), difference 4.3% (0.0% to 8.7%), P=0.05, and adjusted for varenicline use was 1.32 (1.08 to 1.62) P=0.007. At 12 months the odds ratio was 1.28 (0.97 to 1.69), difference 2.7% (-0.4% to 5.8%), P=0.09 unadjusted for varenicline use and after adjustment was 1.36 (1.02 to 1.80) P=0.04. 5.9% of participants discontinued preloading owing to intolerance. Gastrointestinal symptoms-chiefly nausea-occurred in 4.0% (2.2% to 5.9%) more people in the preloading arm than control arm. Eight serious adverse events occurred in the preloading arm and eight in the control arm (odds ratio 0.99, 0.36 to 2.75).ConclusionsEvidence was insufficient to confidently show that nicotine preloading increases subsequent smoking abstinence. The beneficial effect seems to have been masked by a concurrent reduction in the use of varenicline in people using nicotine preloading, and future studies should explore ways to mitigate this unintended effect.Trial registrationCurrent Controlled Trials ISRCTN33031001.
| S-EPMC5998048 | biostudies-literature